Erschienen:
Springer Science and Business Media LLC, 2021
Erschienen in:
Scientific Reports, 11 (2021) 1
Sprache:
Englisch
DOI:
10.1038/s41598-021-84042-x
ISSN:
2045-2322
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic bile ducts are destroyed by an autoimmune reaction. Our previous genome-wide association study (GWAS) identified chromosome 11q23.1 as a susceptibility gene locus for PBC in the Japanese population. Here, high-density association mapping based on single nucleotide polymorphism (SNP) imputation and in silico/in vitro functional analyses identified rs1944919 as the primary functional variant. Expression-quantitative trait loci analyses showed that the PBC susceptibility allele of rs1944919 was significantly associated with increased <jats:italic>COLCA1</jats:italic>/<jats:italic>COLCA2</jats:italic> expression levels. Additionally, the effects of rs1944919 on <jats:italic>COLCA1</jats:italic>/<jats:italic>COLCA2</jats:italic> expression levels were confirmed using genotype knock-in versions of cell lines constructed using the CRISPR/Cas9 system and differed between rs1944919-G/G clones and -T/T clones. To our knowledge, this is the first study to demonstrate the contribution of <jats:italic>COLCA1/COLCA2</jats:italic> to PBC susceptibility.</jats:p>